1. Field of the Invention
This invention relates to a novel process for producing cephalosporin derivatives and novel cephalosporanic acid derivatives. More particularly, this invention relates to an improved process for producing 7-isocyanatocephalosporin derivatives represented by the formula (III) above, which are known to be useful as intermediates for the preparation of cephalosporin derivatives having an excellent antimicrobial activity; to novel 7-amino-3-desacetoxycephalosporanic acid derivatives represented by the formula (II) above, which are useful as intermediates for the preparation of cephalosporin derivatives of the formula (III) above; and to novel penicillin derivatives of the formula (I) above, which can advantageously be used as starting materials for the preparation of the 7-isocyanatocephalosporin derivates represented by the formula (III) above.
2. Description of the Prior Art
It is well known that 7-isocyanatocephalosporin derivatives represented by the formula (III) can be produced from 7-amino-3-desacetoxycephalosporanic acid derivatives as disclosed in Belgian Pat. No. 760,494 and that a wide variety of cephalosporin compounds having a broad spectrum of antimicrobial activity and thus being useful as antibacterial agents can be prepared in the manner described in Belgian Pats. Nos. 760,494 and 775,011, Netherlands Pats. Nos. 7,208,149, 7,205,885, 7,200,486, 7,018,385 and 7,209,964, and German Pat. No. 2,155,081 by taking advantage of the known reactivity of an isocyanate group of the 7-isocyanatocephalosporin derivatives. It is also well known that 6.beta.acylamidopenicillin sulfoxides can be converted into 7.beta.-acrylamidocephalosporin derivatives by heating the 6.beta.-acylamidopenicillin sulfoxides at a temperature ranging from about 100.degree. C to about 175.degree. C in the presence of an acidic compound as disclosed in U.S. Pat. No. 3,275,626. However, it has not been hitherto known that phosphoric acid amide compounds are generally converted into corresponding isocyanate compounds by treatment with phosgene via dephosphorylation.
However, cephalosporin derivatives having various acyl groups cannot be prepared by converting 6.beta.-acylamidopenicillin sulfoxide derivatives into 7.beta.-acylamidocephalosporin derivatives as disclosed in U.S. Pat. No. 3,275,626. For example, investigations by the present inventors revealed that penicillin sulfoxide derivatives having an ureido group as a side chain can not be used to produce the corresponding cephalosporin derivatives by the procedure taught in U.S. Pat. No. 3,275,626.
An object of the present invention is therfore to provide an improved process for producing the cephalosporin derivatives represented by the formulae (II) and (III).
Another object of this invention is to provide novel 7-amino-3-desacetoxycephalosporanic acid derivatives represented by the formula (II) as hereinbefore defined.
A further object of this invention is to provide novel penicillin derivatives of the formula (I) as hereinbefore defined.
Other objects of the present invention will be apparent from the following description.